In the recent years, the existence of cardiac regeneration in mammalian models and even humans has been confirmed in several,
carefully designed and executed studies. However, the intrinsic rate of cardiomyocyte renewal is not sufficient to replenish the large
number of cells lost after a major injury in the heart, such as myocardial infarction. Therefore, exogenously administered cells with progenitor
properties have been used in order to augment this process. From the several candidate cell populations, cardiac derived progenitor
cells appear particularly attractive for this purpose, based on data from many experimental studies but also preliminary clinical applications.
Cardiosphere-derived cells are a mixed cell population that has shown great potential in stimulating endogenous mechanisms of
cardiac repair and attenuating adverse remodeling of the heart. In the present review, we discuss in detail the existing evidence regarding
the therapeutic role of cardiosphere-derived progenitor cell administration in the post-myocardial infarction setting. Proof-of-concept
studies in rodents, as well as more clinically relevant experiments in large animal models, have provided consistent results regarding the
potential of these cells to improve cardiac structure and function after myocardial infarction. Existing data about the underlying mechanisms
that are implicated in myocardial regeneration triggered by these cells are presented, as well as preliminary data from clinical applications
and future perspectives of this novel therapeutic option.